Photoredox‐Catalyzed Site‐Selective α‐C(sp³)−H Alkylation of Primary Amine Derivatives

Abstract

The synthetic utility of tertiary amines to oxidatively generate a-amino radicals is well established, however,p rimary amines remain challenging because of competitive side reactions.T his report describes the site-selective a-functionalization of primary amine derivatives through the generation of a-amino radical intermediates.Employing visible-light photoredox catalysis,p rimary sulfonamides are coupled with electron-deficient alkenes to efficiently and mildly construct CÀCbonds.Interestingly,adivergence between intermolecular hydrogen-atom transfer (HAT) catalysis and intramolecular [1,5] HATwas observed through precise manipulation of the protecting group.T his dichotomyw as leveraged to achieve excellent a/d site-selectivity.

Photocatalytic methods for amino acid modification

“…8). 25 Using a trifluoromethylsulfonamide (triflamide) protecting group for the side-chain amine, addition of tert-butyl acrylate at the carbon a to the e-amine was demonstrated. After excitation of an iridium catalyst, single electron oxidation of quinuclidine forms an intermediate capable of performing hydrogen atom transfer (HAT) with the a-carbon, thereby producing the radical anion of the sulfonamide.…”

Recent Advances in Rapid Synthesis of Non-proteinogenic Amino Acids from Proteinogenic Amino Acids Derivatives via Direct Photo-Mediated C–H Functionalization

“…Additionally, the installed bis(phenylsulfonyl)ethylene group was a helpful synthetic intermediate for further versatile transformations. Later in 2019, Rovis's group also reported an example of photo-mediated functionalization of the lysine derivative with tert-butyl acrylate in 58% yield with 1:1 dr value (Scheme 9b) [35]. Notably, the authors have tested other Electron-deficient olefins were also investigated as alkylation reagents employed in the photo-mediated C(sp 3 )-alkylation of amino acids.…”

“…Additionally, the tinstalled bis(phenylsulfonyl)ethylene group was a helpful synthetic intermediate for further versatile transformations. Later in 2019, Rovis's group also reported an example of photo-mediated functionalization of the lysine derivative with tert-butyl acrylate in 58% yield with 1:1 dr value (Scheme 9b) [35]. Notably, the authors have tested other protecting groups such as the trifluoroacetyl group, p-toluenesulfonyl group, and acetyl group, and they are all deleterious to this process, which indicated that the trifluoromethanesulfonyl group as the protecting group on the nitrogen atom was extremely essential to the reaction.…”

Advances in C(sp3)–H Bond Functionalization via Radical Processes

“…In 2019, Rovis and co-workers reported the site-selective -functionalization of primary amines through the generation of -amino radical intermediates (Scheme 59). 56 Employing visible-light photoredox catalysis, primary sulfonamides were coupled with electron-deficient alkenes to form C-C bonds. Interestingly, a divergence between intermolecular HAT catalysis and intramolecular 1,5-HAT was observed via accurate manipulation of the protecting group.…”